Engineered MEVs for photoreceptor-targeted delivery of USP25 to alleviate diabetic retinopathy.

ABSTRACT: Diabetic retinopathy (DR) is the major cause of vision decline in adults worldwide. Photoreceptor loss is considered a main pathogenesis of retinal dysfunction in DR. Recently, mesenchymal stem cell-derived extracellular vesicles (MEVs) treatment has been considered a promising cell-free approach for retinal disorders. However, the role and mechanism of MEVs in alleviating photoreceptor injury in DR remain unclear. In this study, MEV treatment improved retinal function and inhibited photoreceptor apoptosis in db/db mice. Mechanistically, the deubiquitinating enzyme ubiquitin-specific peptidase 25 (USP25) in MEVs was responsible for the MEV-mediated photoreceptor therapy by inhibiting hyperglycemia-induced αA-crystallin (CRYAA) ubiquitination. Moreover, USP25-enriched MEVs modified with the

SUBMITTER: Sun Y 

PROVIDER: S-EPMC12366390 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature